Abstract A major obstacle to the development of protective therapies for polycystic kidney disease (PKD) has been our limited understanding of the cellular pathways that are altered when the PKD1 (polycystin-1 or PC1), PKD2 (polycystin-2 or PC2) or PKHD1 (polyductin or PD1) genes (collectively referred to as PKD genes/proteins) are mutated. In general, researchers have identified critical cellular pathways in cell culture systems and in animal models, and then sought druggable components of these pathways with the goal of developing therapeutic agents that would slow disease progression. This paradigm requires a basic tool kit of validated PKD reagents that includes antibodies, DNA constructs and cell lines. Although some tools are available at a few centers in the US, investigators frequently have limited access to them. There is an unmet need in the PKD Research Community for validated and readily available PKD reagents. In addition, many investigators who are new to the field may not have the experience to leverage these tools for in-depth analysis of PKD proteins. The main objective of Core B is to meet these needs by providing a comprehensive set of validated PKD reagents along with technical assistance. This takes advantage of expertise that we have established over the past two decades and a reagent repository that we have significantly expanded during the last funding period. Core B is comprised of two highly integrated components. The ?antibody validation? component will provide validated PC1 and PD1 antibodies coupled with expert advice on how to use the reagents. Furthermore, we will develop novel PC1 and PD1 antibodies that have the highest specificity against native protein using a novel strategy (folded domain antigens). The ?vectorology? component will allow investigators immediate access to an extensive collection of plasmid expression vectors for wild type and mutant PKD proteins and CRISPR PKD genome-editing vectors, and offer custom PKD expression vectors with newly developed tags and/or engineered mutations. We will also provide isogenic MDCK and IMCD cell lines that express these proteins in a stable and inducible fashion. The Core will also assist our research base with utilization of our reagents. The Specific Aims are: Aim 1: To provide a panel of validated PC1 antibodies that can detect endogenous proteins. Aim 2: To provide a panel of validated PD1 antibodies that can detect endogenous proteins. Aim 3: To provide PKD expression vectors and CRISPR genome-editing vectors. Aim 4: To provide renal cell models with stable and inducible expression of PKD proteins, and with PKD gene knockouts. Aim 5: To provide a training workshop in PKD protein biochemistry. In summary, the mission of Core B is to effectively remove technical barriers to PKD research in order to promote discoveries that will facilitate the development of protective therapies for PKD.